Double heterozygotes of HbE and α-Thalassemia-1 (Southeast Asian type) ((β/β, - -SEA/αα) can result in severe thalassemia conditions, such as HbE/β-thalassemia (β/β)) and Hb Bart's hydrops fetalis syndrome (- -/- -). Identification of these double heterozygotes is crucial for preventing births affected by Hb Bart's hydrops fetalis syndrome. The most accurate method for detecting HbE/SEA-α-Thalassemia-1 double heterozygotes is PCR-based analysis, which is complex and costly. This study aimed to develop a hematologic algorithm for predicting double heterozygotes of HbE/SEA-α-Thalassemia-1. A retrospective analysis was conducted on 471 datasets of red blood cell indices and HbE levels collected from hospitals in Northern Thailand. Data analysis and algorithm development were performed using statistical tools and software. The prevalence of HbE/SEA-α-Thalassemia-1 double heterozygotes was 12.1%. Significant differences were found in HbE levels, MCV, MCH, and RBC count between single HbE heterozygotes and HbE/SEA-α-Thalassemia-1 double heterozygotes. The predictive algorithm, named the ',' was established as follows: HbE ≤ 20.5%; RBC > 4.55 × 10/µL; and MCV ≤ 70.5 fL. This algorithm demonstrated 40% sensitivity (95% CI: 30.3-50.3), 100% specificity (95% CI: 96.4-100), 100% positive predictive value (95% CI: 96.4-100), 95.6% negative predictive value (95% CI: 90.0-98.9), a negative likelihood ratio of 0.6 (95% CI: 0.3-1.2), an infinite positive likelihood ratio, 95.7% accuracy (95% CI: 90.1-98.9), and an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) for identifying HbE/SEA-α-Thalassemia-1 double heterozygotes. Therefore, the '' is a valuable clinical tool to support accurate identification of the double heterozygotes of HbE and SEA-α thalassemia 1.

Thalassemia is one of the most common inherited red blood cell disorders worldwide and is regarded as a major public health concern in Thailand and many countries. Thalassemia prevention and control in Thailand will face greater challenges due to the entrance of the ASEAN Economic Community (AEC) workers migrating to the country. This study examined the prevalence of thalassemia among migrant workers from Cambodia and Myanmar. Thalassemia was identified through the analysis of hemoglobin (Hb) and DNA. Out of 532 blood samples, 60.5% were found to be thalassemia heterozygotes or affected by the disease, encompassing 21 different thalassemia genotypes. The prevalence of homozygous (7.4%) and heterozygous (29.8%) Hb E was high among workers from Cambodia. Among workers from Myanmar, the prevalence of α-thalassemia is interestingly high, reaching an unprecedented 46.1% in total. The prevalence of β-thalassemia heterozygotes is 3.2%. The molecular information obtained should provide useful data for improving diagnostics, as well as for planning prevention and control programs for severe thalassemia and genetic counseling among migrant workers in Thailand.

The coexistence of β-thalassemia major and Type 3 von Willebrand Disease (VWD) is an exceptionally rare clinical phenomenon. We describe a 3-year-old female with genetically confirmed β-thalassemia major due to an frameshift mutation (exons 8-9) and Type 3 VWD with von Willebrand factor (VWF) antigen at 1.8%. Clinically, she presented with recurrent epistaxis, anemia, and transfusion dependence. Serial laboratory investigations revealed persistent microcytic hypochromic anemia, iron overload (ferritin 1778 ng/mL), and markedly low VWF antigen. Management included red blood cell transfusions, chelation, hydroxyurea, vitamin supplementation, and supportive care, while balancing the bleeding risks from VWD. This report underscores the diagnostic challenge and therapeutic complexity of overlapping congenital anemia and bleeding disorder. Multidisciplinary care and genetic testing were pivotal in confirming the diagnosis and guiding management.

α-Thalassemia is a common genetic disorder marked by a reduced synthesis of α-globin chains, leading to varying degrees of anemia. In this study, we describe a novel variant, c.305T > C (Leu > Pro), identified through next-generation sequencing (NGS) genomic screening. The proband, a 6-year-old female, presented with low hemoglobin levels (103 g/L) and microcytic anemia (MCV 58.6 fL, MCH 17.7 pg). To confirm the presence of this variant, Sanger sequencing was utilized, validating the heterozygous substitution of thymine for cytosine at nucleotide position 305 in the α-globin gene. Family studies indicated that this novel variant was inherited from the father, who also exhibited hematological indicators consistent with thalassemia (MCH 26.6 pg). Furthermore, the proband was found to carry a common β-thalassemia mutation at Codon 17 (A > T), inherited from her mother. Our findings highlight the clinical relevance of the c.305T > C variant in the context of β-thalassemia, emphasizing the need for comprehensive phenotypic evaluations to elucidate the implications of novel mutations in thalassemia.

Thalassemia is associated with high morbidity and mortality. The purpose of this study was to delineate the genetic mutation spectrum of thalassemia in Huadu District, Guangzhou, to provide a basis for prenatal diagnosis and genetic counseling. Between January 2020 and December 2024, 2,428 blood samples from individuals with suspected thalassemia were collected at Huadu District People's Hospital. α- and β-Thalassemia genotypes were identified using gap-polymerase chain reaction (Gap-PCR) and PCR-reverse dot blot (PCR-RDB). Overall, 1,774 (73.06%) patients tested positive for thalassemia. Of these, 52.37% (929/1,774) had α-thalassemia, 42.00% (745/1,774) had β-thalassemia, and 5.64% (100/1,774) had co-inheritance of α/β-thalassemia. The most frequent α-thalassemia genotype was (--/αα) seen in 62%. β-Thalassemia was dominated by high-frequency mutations, including β/β (270 cases, 36.91%) and β/β (26.98%). The most typical combined genotype was --/αα with β/β (18%). The mutation profile in Huadu District aligns with the Southern Chinese thalassemia spectrum but exhibits regional specificity, mirroring the overall epidemiological pattern of Southern China while demonstrating distinct regional mutation clusters. Greater emphasis should be placed on thalassemia screening, genetic counseling, and prenatal diagnosis to improve birth outcomes.

Advances in transfusion and chelation have improved survival in transfusion-dependent thalassemia major (TDT), yet cumulative iron toxicity can impair endocrine function. We evaluated whether pituitary iron detected by MRI is associated with endocrine outcomes. Medical records of 60 pediatric TDT patients (mean age 11.5±4.4 years) were reviewed. Iron burden was estimated using serum ferritin and liver iron concentration (LIC) measured by R2 MRI. Pituitary iron was assessed on 1.5-T MRI with coronal and axial sequences using a signal intensity ratio (SIR) method, placing regions of interest in the pituitary gland and nasopharyngeal fat. Endocrine outcomes included short stature, thyroid dysfunction, and hypogonadism. Short stature was present in 25 patients (41.7%), subclinical hypothyroidism in 5 (8.3%), and hypogonadism in 9 (15%). Among 54 patients who underwent liver R2 MRI, 40 (74%) had no iron overload and 14 (26%) had mild accumulation. Neither serum ferritin nor LIC correlated with endocrine complications. Additionally, LIC did not correlate with the pituitary/fat SIR. Overall, the SIR method showed limited diagnostic utility and low specificity for assessing pituitary iron deposition. In this single-center pediatric cohort, pituitary SIR did not reflect hepatic iron load or predict endocrine morbidity. Given these limitations, quantitative T2/T2* techniques may offer greater accuracy for detecting pituitary iron overload. Larger, multicenter studies are warranted to validate the clinical relevance of pituitary MRI in the assessment of endocrine dysfunction in TDT.

α-Thalassemia is a prevalent genetic disorder, and recent global migration has increased the need for effective screening and diagnosis, even in historically low-prevalence regions. Accurate diagnosis of symptomatic individuals and carriers is essential for appropriate management. This multi-year retrospective study presents 776 cases correlating CBC parameters, hemoglobin fractionation, α-globin gene deletion/duplication analysis, and complete α-globin sequencing. Among these cases, 174 (22%) had abnormal Hb fractionation patterns by HPLC, and 602 (78%) had normal pattern. By deletion/duplication analysis, 576 (74%) had an intact α-globin gene cluster, while deletions were detected in 24% (188/776) of cases; 103 (13%) with one-gene, 82 (11%) two-gene, 3 (0.3%) with three-gene deletions, and 12 (1.5%) had α- gene triplication. Sequencing identified variant hemoglobin in 198 (26%) samples, including 163 α-globin variants, the remaining 36 variants were either β or delta globin variants. Notably, 28 α-globin variants were undetectable by HPLC/CE, 18 of which were non-deletional or 'thalassemic' variants. A total of 72 (9.3%) samples were found to have combined α-globin gene deletion and an α-globin variant. CBC parameters showed no significant differences between normal individuals and those with one or more α-gene deletions or non-deletional α-globin variants. EMQN thresholds demonstrated 81% sensitivity and 25% specificity for detecting deletional α-thalassemia. Our findings highlight the utility of molecular analysis for carrier detection and the necessity of α-globin full gene sequencing in cases with unexplained clinical phenotypes.

Non-transfusion-dependent thalassemias (NTDT), including thalassemia intermedia (TI), are often perceived as less severe than their transfusion-dependent counterparts. However, they impose a significant health burden, manifesting in complications such as splenomegaly, iron overload, skeletal deformities, and cardiopulmonary diseases. This case report aims to enhance understanding of the complexities associated with NTDT, particularly regarding the rapid progression of infection and the associated challenges in management. We report the case of a 62-year-old male farmer from a high-incidence region of thalassemia in China. He was diagnosed with αNTDT during a medical evaluation. His baseline hemoglobin levels were 7 g/dL at the time of genetic testing for thalassemia and 7.2 g/dL upon hospital admission prior to infection. His clinical phenotype was classified as thalassemia intermedia. The patient presented with significant comorbidities, including chronic anemia, iron overload, and pulmonary hypertension, which contributed to his rapid clinical deterioration. Within two months of his definitive diagnosis, the patient developed sepsis that rapidly progressed to multiple organ dysfunction syndrome, leading to death 43 h after admission. Sepsis in patients with NTDT progresses rapidly and is associated with a high mortality rate, primarily due to the compounded burden of chronic anemia, iron overload, and immune dysfunction. This case highlights the need for increased clinical awareness to facilitate early diagnosis and prompt management, even in αNTDT, which is generally considered a milder disorder compared to βNTDT. Enhancing community awareness and implementing proactive healthcare strategies, particularly in high-incidence areas, may significantly reduce adverse health outcomes in patients with NTDT.

HbH disease may rarely be caused by a combination of deletional α-thalassemia and an unstable α-globin chain variant. Diagnosis is challenging and may be delayed in cases with mild symptoms. Hemoglobin Dubai is an unstable α-globin chain variant that was previously reported to be asymptomatic. We report the case of a 74-year-old man with mild HbH disease due to compound heterozygosity for Hemoglobin Dubai with deletional α-thalassemia.

We describe the identification of an intronic variant in the β-globin gene (: c0.92 + 9C > T) in a 41-year-old Spanish male presenting with microcytosis and hypochromia in the absence of iron deficiency. This variant, located in intron 1 of the gene, was identified using the Devyser Thalassemia NGS kit and confirmed by Sanger sequencing. In silico predictions suggest potential splicing disruption. The hematological profile was consistent with β-thalassemia trait, although Hb A2 values were within normal ranges. This variant is not reported in public databases and is currently classified as of uncertain significance with moderate pathogenic potential according to ACMG criteria. This discrepancy between bioinformatic predictions and clinical classification is discussed. The variant has been submitted to both HbVar and IthaGenes databases (submission ID pending). This report contributes to the expanding catalog of variants and underscores the diagnostic relevance of intronic regions.

We report a novel δ-chain hemoglobin (Hb) variant, designated Hb A2-Malay [:c.139G > C;316-443A > G], identified in 19 Malaysian Malay individuals. This variant was consistently observed in both Capillary Electrophoresis (CE) Zone 1 and High-Performance Liquid Chromatography (HPLC) S-window analyses. Sanger sequencing revealed a new G > C substitution at the first base of codon 46 within the gene, leading to a glycine to arginine amino acid change. Additionally, a -acting polymorphism, an A to G substitution at intron II position 456, was genotyped in all carriers. Routine genetic testing for common α-thalassemia, using Gap-PCR and Amplification Refractory Mutation System, was also performed. Four carriers exhibiting similar hematological indices were found to have a concomitant heterozygous -α mutation. Furthermore, three β carriers demonstrated higher Zone 1 and S-window percentages.

We report a family study wherein the index patient, a 6-year-old Mozambican female, was diagnosed with compound heterozygous HbS and Hb Maputo. She presented with acute pain, swelling and tenderness in the right fronto-temporal region of the skull, which raised suspicion of sickle cell disease (SCD). Prior to this presentation, a two-year history of vague clinical symptoms (viz., periodic fever, joint pain and abdominal pain) was obtained. Both parents were clinically asymptomatic. Hemoglobin separation studies were performed using hemoglobin electrophoresis and high performance liquid chromatography. Next generation sequencing technology was employed for gene sequencing analysis of globin genes. Both parents were also fully investigated. Hemoglobin separation studies on the index patient detected two hemoglobin variants that were identified on gene sequencing analysis as HbS and Hb Maputo. The mother and father were demonstrated to have heterozygous HbS and Hb Maputo, respectively. The α globin genes in all the family members had a normal wild type configuration. Conclusion: Hb Maputo in the heterozygous state is an uncommon β chain variant that is clinically silent whereas co-inheritance of Hb Maputo and HbS causes a sickling disorder with vaso occlusive disease.

Hemoglobin (Hb) Phnom Penh is a rare Hb variant of non-clinical significance caused by a duplication of TCA within exon 3 of the human gene, resulting in the insertion of isoleucine [c.353_355dup (p.Phe118_Thr119insIle)]. This variant can interfere with glycated Hb analysis and has been identified in several Asian populations, including Cambodian, Chinese, northeastern Thai, and Taiwanese individuals. In this study, we identified a northern Thai man with Hb Phnom Penh. The proband was a heterozygote and asymptomatic. The inheritance of Hb Phnom Penh was suspected based on his abnormal Hb pattern observed through high-performance liquid chromatography and confirmed by Sanger sequencing. Additionally, molecular analysis revealed that Hb Phnom Penh exhibits greater instability compared to HbE. Our findings report, for the first time, the presence of Hb Phnom Penh in northern Thailand and its instability, suggesting the heterogeneity of this Hb variant in Thailand and providing further insights into its basic characteristics.

Dominant β-thalassemia is a rare form of thalassemia that is caused by a heterogenous group of molecular defects, including missense, nonsense, and frameshift mutations. Among the missense mutations involving the third exon of β-globin gene is the rare Hb Dieppe () which leads to a very unstable β-variant. In the current study we report this variant in an 8-year-old girl and her 35-year-old mother in an Iraqi Kurdish family, both presenting as β-thalassemia intermedia with moderate hypochromic anemia, increased hemoglobin F and borderline hemoglobin A2. This constitutes the first report of this variant from an Eastern Mediterranean country, and underscores the pivotal role of molecular studies to diagnose Hb Dieppe and other dominant β-thalassemias, since in most cases the resultant variants are undetectable by hemoglobin electrophoresis.

Sickle cell-β-thalassaemia (Hb S/β-thal) results from the compound heterozygosity of sickle cell and β-thalassaemia alleles. The influence of α-globin genotypes on clinico-hematological and biochemical parameters in 404 cases of Hb S/β-thal with IVS I-5 (G→C) (: c.20A > T/: c0.92 + 5G > C) mutation was studied. Normal α-globin genotype (αα/αα), heterozygous α-thal (-α/αα) and homozygous α-thal (-α/-α) were found in 204 (50.5%), 114 (28.22%), and 86 (21.29%) cases respectively. The overall incidence of α-thal was found to be 49.5% and allele frequencies for α and α α-thal were found to be 0.23 and 0.11 respectively. RBC count, total hemoglobin and hematocrit levels were significantly higher in homozygous α-thal, intermediate in heterozygous α-thal and lower in normal α-globin genotype. Painful events per year, requirement of blood transfusion per year and hospitalization per year did not show any significant differences across these α-globin genotypes, although, the requirement of blood transfusion per year and hospitalization per year were more in patients with normal α-globin genotypes. Asymptomatic cases were higher in prevalence among homozygous α-thal (9.3%) compared to the other two groups. The age at clinical presentation was marginally later than that among other two groups. The present study shows quite high prevalence of α-thal trait among patients with Hb S/β-thal with IVS I-5 (G→C) mutation. Although influence of homozygous α-thal was found to have some protection further follow up and studies are needed to find its significance.

Beta-thalassemia is a hereditary hemoglobinopathy characterized by significant clinical variability, largely influenced by the underlying genetic mutations. We report a 47-year-old female patient with β-thalassemia intermedia harboring a rare homozygous mutation in the β-globin gene promoter: :c.-136C > G (-86 C > G). The patient showed marked clinical response to hydroxyurea therapy with a notable increase in hemoglobin levels, reduction in spleen size and improvement of fatigue and bone pain due to extramedullary hematopoiesis. This report highlights the role of genetic characterization in understanding rare forms of thalassemia and the potential of hydroxyurea as a personalized treatment strategy for patients with unique genetic determinants.

Sickle cell disease (SCD) is the most common hemoglobinopathy, affecting approximately 300,000 newborns worldwide each year. Hematopoietic stem cell transplantation (HSCT) is the only current curative option for the disease. Still, it is hindered by the availability of suitable donors, socio-economic issues, transplant failure and long-term complications of transplant, including graft-versus-host disease-acute and chronic. To date, there is no standardized protocol for conditioning regimens in SCD patients. A total of 100 pediatric patients diagnosed with sickle cell disease (SCD) underwent allogeneic hematopoietic stem cell transplantation (HSCT) between January 2015 and December 2024. Fifty-five patients (59.8%) underwent HLA-identical sibling-donor, and 37(40.2%) underwent haploidentical transplants. Eighty-three (91.2%) had stable engraftment. The median follow-up time was 31.6 months. Overall survival was 86.9%(95% CI: 79.3%-93.4%) in our cohort of 92 patients transplanted for SCD from either HLA-matched siblings or haploidentical donors, with a median follow-up of 53 months, with EFS of 77% without death or rejection. The survival rates were significantly higher in MSD HSCT (53/55, 96.4% vs 27/37, 78.3%,  < 0.01). The outcomes in haploidentical outcomes have significantly improved (2014-2018 vs 2019 to 2023). The cumulative incidence of acute graft-versus-host-disease (GVHD) was 26% (95% CI - 17.9% to 36.8%) and of chronic GVHD was 8.4% (95% CI - 3.7% to 17.1%) at 2-year post-transplant. Viral reactivations were seen in 18 patients. In haploidentical transplants, we gradually drifted toward reduced toxicity conditioning, including Thio-Flu-Cy-TBI-ATG and found better outcomes through the years. The use of post-transplantation (PTCy) has led to a significantly reduced risk of GVHD.

Thalassemia is one of the most prevalent genetic disorders. Blood transfusion, as the main treatment, harbors diverse side effects, including alloimmunization to RBC antigens, exacerbating hemolysis, and blood requirements. The role of miR155, as a regulator of the immune system, was investigated to divulge its role in the production of alloantibodies in thalassemia patients. The antibody screening technique was used to identify TDT patients with alloimmunization against erythrocyte antigens. PBMC were isolated from selected TDT patients and matched controls using the Ficoll-Paque method, and then miRNA was extracted from cells by the TRIzol reagent. Finally, the relative expression of miR155 was measured using the stem-loop RT-PCR technique. One hundred fifty-eight patients with TDT were screened for the presence of alloantibodies, of whom 14 patients were identified to develop alloimmunization against RBC antigens. There was no statistically significant difference between TDT patients with or without alloantibodies (15 age and sex matched non-immunized patients) in terms of the frequencies of splenectomy, vaccination against hepatitis B, blood types, RHD positivity, and various complications. The expression of miR155 was significantly higher in patients with alloantibodies (mean fold change: 4.74 ± 2.76) compared to non-immunized TDT patients (mean fold change: 1.8 ± 0.68,  = 0.002). Our findings indicated that miR155 overexpression can be involved in modulating immune responses and triggering the production of alloantibodies in TDT patients. More studies are required in this field to further elucidate the role of miR155 in alloimmunization of these patients and other conditions associated with this problem.